人甲状旁腺激素(1-34)突变蛋白的设计与活性验证
邱爽;姜曰水;李芝芹;雷楗勇;陈蕴;金坚
【期刊名称】《药学学报》 【年(卷),期】2012(047)007
【摘要】通过对NCBI数据库中不同物种同源序列进行比对protein-protein BLAST,并利用计算机软件Discovery Studi03.1进行分子对接和分子动力学模拟,对天然人甲状旁腺激素(1-34)的3个氨基酸R25K26K27进行Q25E26L27置换,并对突变体的生物活性进行了评价.结果显示:突变后PTH(1-34)-(RKK-QEL)和突变前PTH(1-34)多肽主链叠合后均方根偏差RMSD值为2.509 3,说明两者主链结构构象差异不大；PTH(1-34)-(RKK-QEL)与受体蛋白PTH1R的相互作用能为-599.253 kcal.mol-1,较天然PTH(1-34)的-554.083 kcalmol-1增强7.5％;氢键数目由32对增加至38对；PTH(1-34)-(RKK-QEL)能显著刺激UAMS-32P细胞RANKL基因的表达(P＜0.01),并抑制OPG基因的表达(P＜ 0.01); PTH(1-34)-(RKK-QEL)作用于UAMS-32P和小鼠原代股骨骨髓细胞共培养体系时,能显著刺激破骨细胞的形成(P＜ 0.01),并且活性高于PTH(1-34)标准品.%Through protein-protein BLAST of homologous sequences in different species in NCBI database and preliminary simulating molecular docking and molecular dynamics by computer software discovery studio 3.1, three amino acids R25K26K27 of natural human parathyroid hormone (1-34) with Q25E26L27 were mutated and the biological activity of the mutant peptide was evaluated. Result showed that: root mean superposition deviation RMSD value between PTH (l-34)-(RKK-
人甲状旁腺激素(1-34)突变蛋白的设计与活性验证
